SLX1A

Chr 16

structure-specific endonuclease subunit SLX1A

Also known as: GIYD1

NCBI Gene: 548593 ENSG00000132207 UniProt: Q9BQ83 OMIM: 615822

The SLX1A protein serves as the catalytic subunit of the SLX1-SLX4 structure-specific endonuclease that resolves DNA secondary structures during DNA repair and recombination by cleaving branched DNA substrates and Holliday junctions. Pathogenic variants in SLX1A cause autosomal recessive microcephaly, growth retardation, and retinal degeneration. This gene shows tolerance to loss-of-function variants with relatively low constraint scores.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein that is an important regulator of genome stability. The protein represents the catalytic subunit of the SLX1-SLX4 structure-specific endonuclease, which can resolve DNA secondary structures that are formed during repair and recombination processes. Two identical copies of this gene are located on the p arm of chromosome 16 due to a segmental duplication; this record represents the more centromeric copy. Alternative splicing results in multiple transcript variants. Read-through transcription also occurs between this gene and the downstream SULT1A3 (sulfotransferase family, cytosolic, 1A, phenol-preferring, member 3) gene. [provided by RefSeq, Nov 2010]

OMIM ResearchGenerating clinical summary…

LOEUF 1.16

Clinical Summary— SLX1A

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Population Constraint (gnomAD)

Low constraint (pLI 0.12) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

31 VUS of 35 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.16LOEUF

pLI 0.123

Z-score 1.35

OE 0.37 (0.15–1.16)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.38Z-score

OE missense 0.45 (0.32–0.64)

22 obs / 49.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.37 (0.15–1.16)

0≤0.351.4

Missense OE?0.45 (0.32–0.64)

0≤0.61.4

Synonymous OE?0.25

0≤1.21.6

LoF obs/exp: 2 / 5.4Missense obs/exp: 22 / 49.2Syn Z: 2.66

ClinVar Variant Classifications

35 submitted variants in ClinVar

ClinVar

Classification Summary

VUS31

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	30	1	0	31
Likely Benign	2	0	2	4
Benign	0	0	0	0
Total	32	1	2	35

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

91 pathogenic / likely-pathogenic (of 100) ClinVar copy-number / structural variants overlap SLX1A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →